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Human NK cells comprise two main subsets, CD56bright and CD56dim cells, which differ in function, phenotype, and tissue localization. To further dissect the differentiation from CD56bright to CD56dim cells, we performed ex vivo and in vitro experiments demonstrating that the CD56brightCD16+ cells are an intermediate stage of NK cell maturation. We observed that the maximal frequency of the CD56brightCD16+ subset among NK cells, following unrelated cord blood transplantation, occurs later than this of the CD56brightCD16- subset. We next performed an extensive phenotypic and functional analysis of CD56brightCD16+ cells in healthy donors, which displayed a phenotypic intermediary profile between CD56brightCD16- and CD56dimCD16+ NK cells. We also demonstrated that CD56brightCD16+ NK cells were fully able to kill target cells, both by Ab-dependent cell cytotoxicity (ADCC) and direct lysis, as compared with CD56brightCD16- cells. Importantly, in vitro differentiation experiments revealed that autologous T cells specifically encourage the differentiation from CD56brightCD16- to CD56brightCD16+ cells. Finally, further investigations performed in elderly patients clearly showed that both CD56brightCD16+ and CD56dimCD16+ mature subsets were substantially increased in older individuals, whereas the CD56brightCD16- precursor subset was decreased. Altogether, these data provide evidence that the CD56brightCD16+ NK cell subset is a functional intermediate between the CD56bright and CD56dim cells and is generated in the presence of autologous T CD3+ cells. [ABSTRACT FROM AUTHOR]

60–70% of AML patients have an indication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their treatment. Graft versus host disease (GvHD), the major cause of mortality and comorbidities post-transplantation, develops by immunological mechanism and decides greatly prognosis and quality of life (QoL) of graft recipient. Current GvHD prophylaxis is not personalized. Infections, toxicities and leukemic infiltration complicate the first chemotherapy phases prior to allo-HSCT. They, to certain extent, induce local immune stimulation. Impact of immune stimulation of this period on incidence of GvHD has not been evaluated. We retrospectively studied 238 AML patients transplanted at first remission from 21 French centers in the ALFA-0702 protocol and found that cutaneous and digestive immune stimulation during induction increases the incidence of skin and gut aGVHD, respectively. Furthermore, prolonged febrile duration correlates with elevated incidence of grade II–IV aGvHD. Thus, we identified a group of patients with higher risk of aGvHD. The benefit of personalized GvHD prophylaxis should be explored in a prospective cohort to decrease incidence of aGvHD in these patients and improve their QoLs. [ABSTRACT FROM AUTHOR]

: We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults. Agence Nationale Recherche contre le Sida (ANRS)0001S–COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized. We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2–43.0], 57.4% [95% CI, 48.1–66.3] and 77.1% [95% CI, 65.6–86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9–65.2) (vs. 32.3% [95% CI, 16.7–51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9–85.7) (vs. 56.1% [95% CI, 46.2–65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies. A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies. [ABSTRACT FROM AUTHOR]

We explored the molecular evolution of the spike gene after the administration of anti-spike monoclonal antibodies in patients with mild or moderate forms of COVID-19. Four out of the 13 patients acquired a mutation during follow-up; two mutations (G1204E and E406G) appeared as a mixture without clinical impact, while the Q493R mutation emerged in two patients (one receiving bamlanivimab and one receiving bamlanivimab/etesevimab) with fatal outcomes. Careful virological monitoring of patients treated with mAbs should be performed, especially in immunosuppressed patients. [ABSTRACT FROM AUTHOR]